. PROJECT SUMMARY (See instructions): The Integrative Physiology Core is designed to conduct in vivo and in vitro experiments and analytical assays to characterize metabolic phenotypes of transgenic/knock-out mouse models potentially useful for understanding diabetes, its complications, obesity and related metabolic diseases or conditions. The primary purpose of the integrative physiology core is to provide comprehensive standardized in vivo and in vitro procedures, accuracy of sample and data analysis, assistance in the design of experiments and interpretation of results to better understand the mechanisms of diabetes, its complications, obesity and related metabolic diseases or conditions for NIH grantees and others, both inside and outside the institution, who wish to characterize metabolic and physiologic alterations that may occur in mice. The Integrative Physiology Core provides highly skilled staff and state-of-the-art instrumentation to provide the most accurate, precise and reproducible in vivo glucose-insulin clamp results with the highest success rate. The principal functions of the Integrative Physiology Core are to provide NIH grantees and others, both inside and outside Yale, a state-of-the-art centralized facility for: 1) In Vivo assessment of insulin action and b-cell function in awake and unrestrained mice using hyperinsulinemic-euglycemic clamp and hyperglycemic clamp experiments, respectively, 2) In Vivo assessment of counter regulatory responses to hypoglycemia, 3) In Vivo assessment of muscle mitochondrial function by ^V and C NMR spectroscopy, 4) Implementation of exercise/training via swimming or treadmill models to assess the metabolic effects of exercise on glucose metabolism. 5) Access to state-of-the-art metabolic mouse imaging by SPECT/PET and MRI, 6) Assessment of transgenic/knockout mouse activity, food and water consumption, and energy expenditure using comprehensive mouse metabolic cages (Columbus Instruments), 7) Preparation of mouse tissue extracts and plasma samples for biochemical (GC-MS, LC/MS/MS, NMR) and molecular analysis in collaboration with the Yale MMPC Metabolomics Core, 8) Performance of in vivo analysis of body composition in mice using Proton NMR spectroscopy, 9) Preparation and characterization of glucose uptake in isolated epitrochelaris muscle, 10) Determination of rates of glucose-stimulated insulin secretion from isolated pancreatic islets, 11) Evaluation of substrate oxidative and non-oxidative metabolism in mouse hepatocyte suspensions, 12) Assistance in the design of in vivo and in vitro experiments and interpretation of in vivo and in vitro experiment results